PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas

Zheng, H. W., Ying, H. Q., Wiedemeyer, R., Yan, H. Y., Quayle, S. N., Ivanova, E. V., Paik, J. H., Zhang, H. L., Xiao, Y. H., Perry, S. R., Hu, J., Vinjamoori, A., Gan, B. Y., Sahin, E., Chheda, M. G., Brennan, C., Wang, Y. A., Hahn, W. C., Chin, L., DePinho, R. A. (May 2010) PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas. Cancer Cell, 17 (5). pp. 497-509. ISSN 1535-6108

URL: http://www.ncbi.nlm.nih.gov/pubmed/20478531
DOI: 10.1016/j.ccr.2010.03.020

Abstract

A hallmark feature of glioblastoma is its strong self-renewal potential and immature differentiation state, which contributes to its plasticity and therapeutic resistance. Here, integrated genomic and biological analyses identified PLAGL2 as a potent protooncogene targeted for amplification/gain in malignant gliomas. Enhanced PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell differentiation while promoting their self-renewal capacity upon differentiation induction. Transcriptome analysis revealed that these differentiation-suppressive activities are attributable in part to PLAGL2 modulation of Wnt/beta-catenin signaling. Inhibition of Wnt signaling partially restores PLAGL2-expressing NSC differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics in malignant cells.

Item Type: Paper
Uncontrolled Keywords: TUMOR-INITIATING CELLS BETA-CATENIN HUMAN GLIOBLASTOMA SELF-RENEWAL SPORADIC MEDULLOBLASTOMAS PATHWAY ACTIVATION PROGENITOR CELLS BRAIN-TUMORS CANCER-CELLS DISEASE Oncology Cell Biology
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL labs > Zheng lab
Depositing User: Matt Covey
Date: May 2010
Date Deposited: 22 Aug 2014 18:51
Last Modified: 22 Aug 2014 18:51
PMCID: PMC2900858
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30700

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